Abstract
Accurate determination of the evolutionary relationships between genes is a foundational challenge in biology. Homology—evolutionary relatedness—is in many cases readily determined based on sequence similarity analysis. By contrast, whether or not two genes directly descended from a common ancestor by a speciation event (orthologs) or duplication event (paralogs) is more challenging, yet provides critical information on the history of a gene. Since 2009, this task has been the focus of the Quest for Orthologs (QFO) Consortium. The sixth QFO meeting took place in Okazaki, Japan in conjunction with the 67th National Institute for Basic Biology conference. Here, we report recent advances, applications, and oncoming challenges that were discussed during the conference. Steady progress has been made toward standardization and scalability of new and existing tools. A feature of the conference was the presentation of a panel of accessible tools for phylogenetic profiling and several developments to bring orthology beyond the gene unit—from domains to networks. This meeting brought into light several challenges to come: leveraging orthology computations to get the most of the incoming avalanche of genomic data, integrating orthology from domain to biological network levels, building better gene models, and adapting orthology approaches to the broad evolutionary and genomic diversity recognized in different forms of life and viruses.
Highlights
Orthology and paralogy are evolutionary relationships linking homologous genes which diverged via speciation or duplication events, respectively (Fitch 1970)
This makes high-quality orthology inference a critical step, with impacts on many downstream analyses ranging from gene functional predictions to biological network interpretation
The latest developments in orthology inference have focused on scalability, community standards, and continuous developments for more integrated benchmarking and towards improved interoperability
Summary
Orthology and paralogy are evolutionary relationships linking homologous genes which diverged via speciation or duplication events, respectively (Fitch 1970). Genomes are shaped by speciation and duplication events, and gene loss, domain architecture rearrangements and horizontal gene transfers, which complexifies orthology predictions and constantly pushes development of new computational methods (Forslund et al 2018). This community effort has led to major achievements, including curated reference proteomes for phylogenetically diverse species (Dessimoz et al 2012), reference species trees useful for orthology predictions (Boeckmann et al 2015) and an online benchmarking service standardizing the assessment and comparison of orthology inference methods (Altenhoff et al 2016).
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